Scientists have uncovered evidence that could change the way doctors think about a common form of stroke and why standard preventive treatments often fail.
New research suggests that lacunar ischemic stroke is not caused primarily by the buildup of fatty plaque within the arteries, as many have assumed. Instead, the strongest link appears to be related to changes in the brain’s own blood vessels, specifically the enlargement and widening of arteries.
The findings may help explain why medications commonly prescribed for stroke prevention, such as aspirin and other antiplatelet drugs, have had limited success in preventing this type of stroke.
Researchers say the results are already helping guide new treatment strategies, including the LACunar Intervention 3 (LACI-3) trial, which is evaluating drugs designed to protect and support the brain’s smallest blood vessels.
Brain small vessel disease and risk of stroke
Lacunar stroke develops when the smallest blood vessels in the brain are damaged by a condition known as small vessel disease. This form of stroke is a major cause of disability and is linked to cognitive decline, dementia, and an increased risk of future strokes. Despite its importance, scientists have struggled to identify exactly what drives the disease, making it difficult to develop effective treatments.
To investigate, researchers from the University of Edinburgh, the UK Dementia Research Institute and international collaborators examined 229 people who had experienced a lacunar stroke or a mild non-lacunar stroke.
Participants received clinical and cognitive evaluations and underwent brain MRIs shortly after their stroke and again a year later. The images allowed scientists to evaluate the type of stroke, monitor for signs of small vessel disease, and identify new areas of brain injury that developed over time.
The team compared two different vascular changes: fatty narrowing of larger arteries and widening and lengthening of arteries within the brain.
Arterial widening emerges as key clue
The analysis showed that narrowing of the large arteries was not associated with lacunar stroke or small vessel disease. While narrowing of the arteries was more common in other forms of stroke, it did not predict new brain damage in follow-up scans.
In contrast, widening of the arteries showed a strong connection with lacunar stroke. Patients with enlarged arteries were more than four times more likely to have suffered a lacunar stroke.
The researchers also found that widening of the arteries was linked to more severe small vessel disease, more rapid progression of brain damage, and a greater chance of developing new “silent” strokes: small areas of damage to brain tissue caused by a disrupted blood supply that can occur without obvious symptoms.
More than one in four participants developed these silent strokes during the study, even though they were receiving standard treatments aimed at preventing additional strokes.
New treatment approaches are being tested
The findings suggest that future therapies should focus on underlying damage affecting small blood vessels in the brain rather than fatty plaque in larger arteries.
Currently, studies such as LACI-3 are investigating whether existing medications, including cilostazol and isosorbide mononitrate, can help protect the brain, reduce the risk of further strokes, and reduce long-term problems related to memory, mobility, and dementia after a lacunar stroke.
Joanna Wardlaw, Professor of Applied Neuroimaging at the Institute of Neuroscience and Cardiovascular Diseases at the University of Edinburgh and group leader at the UK Dementia Research Institute, said: “This study provides strong evidence that lacunar stroke is not caused by a fatty blockage of the larger arteries, but by disease of the small vessels within the brain itself. Recognizing this distinction is crucial, because it explains why conventional treatments such as antiplatelet drugs are not as effective. effective for this type of stroke and highlights the urgent need to develop new therapies that target the underlying microvascular damage.”
The study was published in the journal Circulation. Funding was provided by the UK Dementia Research Institute (funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK), Leducq Foundation, Stroke Association, British Heart Foundation, Scottish Government Chief Scientific Office, Row Fogo Charitable Trust, Wellcome Trust and other national funding agencies. The research team also included scientists from China and Mexico.